Tilajka Álmos, Kurilla Anita, László Loretta, Lovrics Anna, Novák Julianna, Takács Tamás, Buday László, Vas Virag
Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Doctoral School of Biology, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary.
Front Mol Biosci. 2024 Aug 21;11:1414805. doi: 10.3389/fmolb.2024.1414805. eCollection 2024.
Colorectal carcinoma (CRC) has emerged as one of the most widespread cancers and was the third leading cause of cancer-related mortality in 2020. The role of the podosomal protein Tks4 in tumor formation and progression is well established, including its involvement in gastric carcinoma and hepatocellular carcinoma; however, exploration of Tks4 and its associated EMT-regulating interactome in the context of colon cancer remains largely unexplored.
We conducted a comprehensive bioinformatic analysis to investigate the mRNA and protein expression levels of Tks4 and its associated partner molecules (CD2AP, GRB2, WASL, SRC, CTTN, and CAPZA1) across different tumor types. We quantified the expression levels of Tks4 and its partner molecules using qPCR, utilizing a TissueScan colon cancer array. We then validated the usefulness of Tks4 and its associated molecules as biomarkers via careful statistical analyses, including Pearson's correlation analysis, principal component analysis (PCA), multiple logistic regression, confusion matrix analysis, and ROC analysis.
Our findings indicate that the co-expression patterns of the seven examined biomarker candidates better differentiate between tumor and normal samples compared with the expression levels of the individual genes. Moreover, variable importance analysis of these seven genes revealed four core genes that yield consistent results similar to the seven genes. Thus, these four core genes from the Tks4 interactome hold promise as potential combined biomarkers for colon adenocarcinoma diagnosis and prognosis.
Our proposed biomarker set from the Tks4 interactome shows promising sensitivity and specificity, aiding in colon cancer prevention and diagnosis.
结直肠癌（CRC）已成为最常见的癌症之一，是2020年癌症相关死亡的第三大主要原因。足体蛋白Tks4在肿瘤形成和进展中的作用已得到充分证实，包括其在胃癌和肝细胞癌中的作用；然而，在结肠癌背景下对Tks4及其相关的上皮-间质转化（EMT）调节相互作用组的探索仍 largely未被探索。
我们进行了全面的生物信息学分析，以研究Tks4及其相关伴侣分子（CD2AP、GRB2、WASL、SRC、CTTN和CAPZA1）在不同肿瘤类型中的mRNA和蛋白质表达水平。我们使用组织扫描结肠癌阵列，通过qPCR定量Tks4及其伴侣分子的表达水平。然后，我们通过仔细的统计分析，包括Pearson相关分析、主成分分析（PCA）、多元逻辑回归、混淆矩阵分析和ROC分析，验证了Tks4及其相关分子作为生物标志物的有用性。
我们的研究结果表明，与单个基因的表达水平相比，七个检测的生物标志物候选物的共表达模式能更好地区分肿瘤和正常样本。此外，对这七个基因的可变重要性分析揭示了四个核心基因，其产生的结果与七个基因一致。因此，来自Tks4相互作用组的这四个核心基因有望作为结肠腺癌诊断和预后的潜在联合生物标志物。
我们从Tks4相互作用组中提出的生物标志物集显示出有希望的敏感性和特异性，有助于结肠癌的预防和诊断。
